10-68911239-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024045.2(DDX50):​c.632C>T​(p.Ser211Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00029 in 1,595,568 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

DDX50
NM_024045.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94
Variant links:
Genes affected
DDX50 (HGNC:17906): (DExD-box helicase 50) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16246074).
BS2
High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX50NM_024045.2 linkuse as main transcriptc.632C>T p.Ser211Leu missense_variant 4/15 ENST00000373585.8 NP_076950.1 Q9BQ39

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX50ENST00000373585.8 linkuse as main transcriptc.632C>T p.Ser211Leu missense_variant 4/151 NM_024045.2 ENSP00000362687.3 Q9BQ39

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152084
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000855
AC:
20
AN:
233950
Hom.:
0
AF XY:
0.0000866
AC XY:
11
AN XY:
126950
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000174
Gnomad OTH exome
AF:
0.000178
GnomAD4 exome
AF:
0.000304
AC:
439
AN:
1443366
Hom.:
2
Cov.:
31
AF XY:
0.000300
AC XY:
215
AN XY:
717768
show subpopulations
Gnomad4 AFR exome
AF:
0.0000312
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000361
Gnomad4 OTH exome
AF:
0.000639
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000264
Hom.:
0
Bravo
AF:
0.000196
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 28, 2024The c.632C>T (p.S211L) alteration is located in exon 4 (coding exon 4) of the DDX50 gene. This alteration results from a C to T substitution at nucleotide position 632, causing the serine (S) at amino acid position 211 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.062
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.0036
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.86
L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.087
Sift
Benign
0.071
T;.
Sift4G
Benign
0.19
T;T
Polyphen
0.0060
B;.
Vest4
0.39
MVP
0.43
MPC
0.46
ClinPred
0.11
T
GERP RS
5.3
Varity_R
0.13
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139388741; hg19: chr10-70670995; API